The present invention is in the field of enzyme proteins that are related to the lanosterol synthase enzyme subfamily, recombinant DNA molecules, and protein production. The present invention specifically provides novel peptides and proteins that effect protein phosphorylation and nucleic acid molecules encoding such peptide and protein molecules, all of which are useful in the development of human therapeutics and diagnostic compositions and methods.
Many human enzymes serve as targets for the action of pharmaceutically active compounds. Several classes of human enzymes that serve as such targets include helicase, steroid esterase and sulfatase, convertase, synthase, dehydrogenase, monoxygenase, transferase, kinase, glutanase, decarboxylase, isomerase and reductase. It is therefore important in developing new pharmaceutical compounds to identify target enzyme proteins that can be put into high-throughput screening formats. The present invention advances the state of the art by providing novel human drug target enzymes related to the lanosterol synthase subfamily.
Lanosterol Synthase
The novel human protein, and encoding gene, provided by the present invention is related to lanosterol synthase enzymes. Specifically, the protein provided by the present invention is 11 amino acids shorter in exon 4 compared with the art-known lanosterol synthase protein provided in Genbank gi4505027 (see the amino acid sequence alignment of the protein of the present invention against gi4505027 provided in FIG. 2).
Lanosterol synthase enzymes are important for catalyzing the cyclization of squalene-2,3-epoxide lanosterol, which is the parental compound of all mammalian steroids (Young et al., Human Genet May 1996;97(5):620-4). Baker et al. (Biochem Biophys Res Commun Aug. 4, 1995; 213(1):154-60) cloned and characterized the human lanosterol synthase gene and found that it encoded a predicted 83 kDa protein of 732 amino acids; this amino acid sequence shared 36-40% identity with yeast and plant homologues and 83% identity with Rattus norvegicus lanosterol synthase. For a further review of the lanosterol synthase gene/protein, see Sung et al., Biol Pharm Bull October 1995; 18(10):1459-61.
Enzyme proteins, particularly members of the lanosterol synthase enzyme subfamily, are a major target for drug action and development. Accordingly, it is valuable to the field of pharmaceutical development to identify and characterize previously unknown members of this subfamily of enzyme proteins. The present invention advances the state of the art by providing previously unidentified human enzyme proteins, and the polynucleotides encoding them, that have homology to members of the lanosterol synthase enzyme subfamily. These novel compositions are useful in the diagnosis, prevention and treatment of biological processes associated with human diseases.
The present invention is based in part on the identification of amino acid sequences of human enzyme peptides and proteins that are related to the lanosterol synthase enzyme subfamily, as well as allelic variants and other mammalian orthologs thereof. These unique peptide sequences, and nucleic acid sequences that encode these peptides, can be used as models for the development of human therapeutic targets, aid in the identification of therapeutic proteins, and serve as targets for the development of human therapeutic agents that modulate enzyme activity in cells and tissues that express the enzyme. Experimental data as provided in FIG. 1 indicates expression in humans in teratocarcinoma, ovary, uterus, muscle, brain, colon, and hippocampus.